- THERAPEUTIC COMPOUNDS
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A (-)-stereoisomer of formula (I): (formula I), wherein X is H or F; or a pharmaceutically acceptable salt or prodrug thereof, is useful as an anesthetic.
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- Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus
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Streptomyces subrutilus ATCC 27467, when grown on a glucose-containing soyabean medium, produces both 1-deoxymannonojirimycin (DMJ) and 1-deoxynojirimycin (DNJ) in its culture medium. When 1- or 2-[2H]-D-glucose is used, the deuterium label appears at C6 in both alkaloids and the labelling pattern suggests that the first step in the biosynthesis of both DNJ and DMJ is a glucose to fructose isomerisation. Studies with 5-2H]- and 6,6-2H2-D-glucose indicate that oxidation of the 6-position of the glucose/fructose occurs during the biosynthesis and that mannonojirimycin is the first aminosugar to be formed. Mannonojirimycin can then undergo dehydration and reduction to DMJ. Alternatively, epimerisation of mannonojirimycin can occur at C2 to give nojirimycin which is then dehydrated and reduced to DNJ.
- Hardick, David J.,Hutchinson, David W.,Trew, Sally J.,Wellington, Elizabeth M. H.
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p. 6285 - 6296
(2007/10/02)
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- Synthesis, Biological Evaluation, and Preliminary Structure-Activity Considerations of a Series of Alkylphenols as Intravenous Anesthetic Agents
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Following our discovery of the intravenous (iv) anesthetic activity of 2,6-diethylphenol in mice, a series of alkylphenols was examined in this species and the most active analogues were further evaluated in rabbits.The synthesis of compounds which were not commercially available was accomplished by adaptations of standard ortho-alkylation procedures for phenols.Structure-activity relationships were found to be complex, but, in general, potency and kinetics appeared to be a function of both the lipophilic character and the degree of steric hindrance exerted by ortho substituents.The most interesting compounds were found in the 2,6-dialkyl series, and the greatest potency was associated with 2,6-di-sec-alkyl substitution.In particular, 2,6-diisopropylphenol (ICI 35868) emerged as a candidate for further development and has subsequently been shown to be an effective iv anesthetic agent in man.
- James, Roger,Glen, John B.
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p. 1350 - 1357
(2007/10/02)
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